Ms Stanard Mebwe Pachong shall be presenting the public part of her Ph.D. defence at 09:00 on Wednesday, 26 April 2017. Venue: Seminar Room of the Merensky Building for Physics.
T Jacobs, GO Lloyd, J-A Gertenbach, KK Müller-Nedebock, C Esterhuysen, and L Barbour “In situ X-ray Structural Studies of a Flexible Host Responding to Incremental Gas Loading” Angew. Chem. Int. Ed. 51, 4913–4916 (2012).
Stanard Mebwe Pachong joined the group to pursue her PhD on dynamics of networks with active cross-linkers. She was previously at AIMS Senegal.
We are grateful to the Organisation for Women in Science for the Developing World for her generous funding.
Imagine the filaments forming the cytoskeleton of a cell. They are confined within the cell membrane. Not only do these filaments influence how the cell might behave mechanically, but how the filaments behave is coupled to the restricted space in which they grow, arrange or combine into networks. Similarly one can think of polymers inside voids of another material, filling cracks or moving between the fillers in an elastomeric material.
For many years we have been interested in the how geometry and stiffness of polymer chains work together. Mainly, this has been through the development of theoretical tools to describe such systems (see paper with Jerry Percus and Harry Frisch; there are others that will appear here shortly) but also recently through a string of simulations performed with Arash Azari at Stellenbosch University and the Centre for High Performance Computing in South Africa.
In a recent paper we investigated polymers of alternating stiffness all confined within a pore. We observe how polymers become separated due to their stiffness.
Theoretical tools (using field-theoretical methods) allow careful analytical and perturbative ways to understand the role of networking, stiffness and inter- and intra-chain interactions.
Arash Azari, Kristian K. Müller-Nedebock “Entropic competition in polymeric systems under geometrical confinement”, EPL 110 68004 doi:10.1209/0295-5075/110/68004 (alternatively, http://arxiv.org/abs/1408.5312)
We present simulations of alternating copolymers of segments of different stiffness that are confined within regions. Mixtures of different chains then have different arrangements depending on the size of the confining region.
In another paper we shall be addressing related (not identical) systems from a more analytical point of view.
B Loos, J-HS Hofmeyr, KK Müller-Nedebock, L Boonzaaier, C Kinnear in Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging (ed. MA Hayat) 3, 39–56 (Elsevier, 2014). DOI: http://dx.doi.org/10.1016/B978-0-12-405529-2.00002-0
S Banerjee, MC Marchetti, KK Müller-Nedebock “Motor-driven dynamics of cytoskeletal filaments in motility assays” Physical Review E 84 011914 (2011) DOI: http://dx.doi.org/10.1103/PhysRevE.84.011914
Molecular machines are responsible for a variety of non-equilibrium actions. They can make cells themselves move about, and perhaps exhibit fascinating collective motion, and the are responsible, amongst other things, for the transportation of cargo, or play a role in the tightening of the contractile ring during cells division.
A range of molecular motors move along the filamentous structures, microtubules and actin filaments, in the cell. It is interesting and challenging to ask and understand how molecular motors when connected in different ways start modifying the properties of the networks of filaments, or how their functioning alters the mechanical and conformational, and other dynamical properties of a variety of structures.
There is a wide range of interesting introductory articles by various authors, for example, check out this one http://www.nature.com/news/the-physics-of-life-1.19105?WT.mc_id=FBK_NatureNews.
A system with a relatively simple set-up is an array of filaments that move on top of a flat bed of molecular motors, a so-called motility assay. When a large number of motor heads grabs, moves, detaches to a filament, they cause it to move, but also to respond to an applied force. Under certain conditions, we found that an instability occurs [Banerjee, et al.]. Current work is related to dealing with interactions of filaments.
Above: A single filament moving on a surface with tethered motors. Cartoon for physical content of Banerjee paper. (Copyright Kristian Müller-Nedebock)
Stepping mechanism formalism
In the project with Janusz Meylahn we introduced novel ways to formulate the stepping action of motor heads using ideas from dynamical networking theories. We hope to present these results very soon.
Can we think about the tension in contractile rings, given the latest, fascinating experiment on filament orientation and the motors linking the rings? This is part of the project Stanard Mebwe Pachong is investigating in her research.
Contractile rings are formed of actin filaments and molecular machines (and possible other components) to actively pinch of the cell membrane after the division of genetic material. A ring of these filaments forms and then contracts ever more tightly.
We are currently studying these systems using analytical dynamical approaches. These are complemented by some simple Langevin dynamics simulations.
Above: A simulations of the motions of actin filaments (some oriented clockwise and others counter-clockwise) under the action of networking and active forces. Two filaments with opposite orientations have been highlighted. (Copyright Kristian Müller-Nedebock)
When networks of filaments are formed (which is typical of the cytoskeleton) pairs of molecular motor heads, for example, can link different strands in addition (perhaps) to other crosslinks, forming an active gel. In past years two MSc theses on these topics have been completed in the group: a general network formalism (using ideas from equilibrium networks in polymer physics) and a dynamical perspective. The work was done by former members Mohau Mateyisi and Karl Möller.
Dr Ben Loos (Dept of Physiological Sciences at Stellenbosch University) has a long-standing interest in the molecular mechanisms that control cell death susceptibility. His research centres around protein degradative mechanisms and their dynamics, transport and function of mitochondria along tubulin networks and their role in neuronal degeneration and migration. His research group utilizes in vitro models for neuronal protein aggregation storage disorders such as Alzheimer’s disease, to unravel and to direct the complex molecular interplay towards an environment that favours cellular function and survival. He has an equally long-standing interest in high resolution fluorescence-based microscopy techniques, and has managed the Cell Imaging Unit (www.sun.ac.za/saf) for many years. Integral part of his research in physiological sciences is the application of powerful microscopy techniques such as SR-SIM.